An endocrine background to renal carcinoma is suggested by its preponderance in males and by reported remission in some patients treated with the steroid hormones, progesterone or testosterone. Steroid hormones are believed to exert the effect on target tissues (physiologic and malignant) by initial interaction with cytoplasmic receptors for the steroids. Our preliminary studies show that some human renal cell carcinomas contain cytoplasmic steroid receptors and, furthermore, that translocation of the steroid into the nucleus does occur. Therefore, we propose three avenues of investigation: first, a detailed examination of the steroid receptors in renal carcinoma, testing for the presence of cytoplasmic receptors for all major classes of steroids (cortisol, aldosterone, progesterone, testosterone, estradiol), determining the steroid specificity of the receptors and quantitating the affinity of the receptors for the steroid; second, examine all major classes of steroids for uptake by tumor nuclei; third, develop an in vitro system for testing for effects of steroids on DNA, RNA or protein synthesis by the tumor. These studies will be conducted concurrently on portions of human renal cell carcinomas obtained from surgical specimens and on the estrogen-induced renal carcinoma in male hamsters.